A comparison of recurrence rates after discontinuation of second-generation antipsychotic long-acting injectable versus corresponding oral antipsychotic in the maintenance treatment of bipolar disorder: A systematic review

AimThis systematic review and frequentist network meta‐analysis used random‐effects models is conducted to determine whether there are differences in the efficacy, acceptability, tolerability, and safety profiles of brexpiprazole (BRE) and aripiprazole (ARI) for Japanese with major depressive disorder (MDD) who were inadequately responsive to antidepressants.MethodsOutcome measures were scores on the Montgomery Åsberg Depression Rating Scale (primary), the Clinical Global Impression severity scale, and social functioning scale; the non‐response rate; the non‐remission rate; all‐cause discontinuation; discontinuation due to adverse events (DAE); at least one adverse event (1AE); serious adverse event, akathisia; tremor; weight gain.ResultsA literature search identified three double‐blind, randomized, placebo‐controlled trials. These comprised one BRE study (with a 1 mg/day [BRE1] and a 2 mg/day [BRE2]) and two ARI studies (with a 3 mg/day arm and a flexible‐dose arm[within the dosage range approved in Japan]) (n = 1736). Both BRE and ARI demonstrated better efficacy than the placebo. BRE but not ARI had a higher DAE than the placebo. ARI but not BRE had a higher 1AE than the placebo. BRE and ARI had a higher risk of akathisia and weight gain than the placebo. There were no significant differences between BRE and ARI for any of the outcomes. Although BRE1 had good efficacy, it carried risk of weight gain. Although BRE2 also had efficacy, it carried risks of DAE, akathisia, and weight gain. However, the risk of akathisia in BRE2 was reduced by an initial dose of 0.5 mg/day rather than 1.0 mg/day.ConclusionsOverall BRE showed similar utility to ARI and a good risk–benefit balance.

Herein, we aimed to formulate a novel oral disintegrating tablet (ODT) of aripiprazole (ARP) capable of rapid disintegration using a direct compression technique. Different ODTs were fabricated with directly compressible excipients, and their disintegration time, wettability (water absorption ratio and wetting time), and mechanical properties (hardness and friability) were evaluated. The optimized ODT comprised F-Melt® type C, Prosolv® SMCC HD90, and Na croscarmellose (10 mg of ARP in a 130 mg tablet). The ODT with 3.1–5.2 kp hardness exhibited rapid disintegration (14.1–17.2 sec), along with appropriate mechanical strength (friability < 0.24%). In a bioequivalent study in Korean healthy subjects (randomized, single-dose, two-period crossover design, n = 37), the novel ODT offered the equivalent pharmacokinetic profile to that of a conventional immediate release tablet (Otsuka, Abilify®, Japan), despite different disintegration and dissolution profiles. The 90% confidence intervals of the geometric mean test to reference ratios considering the area-under-the-curve and maximum plasma drug concentrations were 1.0306–11051 and 0.9448–1.1063, respectively, satisfying FDA regulatory criteria for bioequivalence. The novel ART ODT was physicochemically stable under the accelerated storage condition (40 °C, RH75%) for 24 weeks. Therefore, the novel ARP-loaded ODT is expected to be an alternative to oral ARP therapy, providing improved patient adherence.

This study presents a simple, rapid, and accurate spectrophotometric method for the determination of Aripiprazole (ARP) in tablets. The determination procedure is based on the reaction of ARP with 7,7,8,8-tet racyanoquinodimethane (TCNQ), producing a colored product that was quantitated spectrophotometrically at 392 nm. Various variables affecting the reaction were optimized. The method exhibited a good linearity range with a correlation coefficient of 0.9994, observed as 0.25–3 μg/mL. The developed method was validated according to the International Council for Harmonisation (ICH) guidelines, assessing specificity, linearity, accuracy, precision, robustness, limit of detection (LOD), and limit of quantitation (LOQ). The formation of the CT-complex and the interaction sites were confirmed by elemental analysis, DSC, IR, and 1H NMR spectroscopy. The method was successfully applied to the determination of ARP in pharmaceutical preparation.

This study presents a simple, rapid, and accurate spectrophotometric method for the determination of Aripiprazole (ARP) in tablets. The determination procedure is based on the reaction of ARP with 7,7,8,8-tet racyanoquinodimethane (TCNQ), producing a colored product that was quantitated spectrophotometrically at 392 nm. Various variables affecting the reaction were optimized. The method exhibited a good linearity range with a correlation coefficient of 0.9994, observed as 0.25–3 μg/mL. The developed method was validated according to the International Council for Harmonisation (ICH) guidelines, assessing specificity, linearity, accuracy, precision, robustness, limit of detection (LOD), and limit of quantitation (LOQ). The formation of the CT-complex and the interaction sites were confirmed by elemental analysis, DSC, IR, and 1H NMR spectroscopy. The method was successfully applied to the determination of ARP in pharmaceutical preparation.

Background and Objectives: Aripiprazole (APZ), an atypical antipsychotic, is mainly prescribed for conditions such as schizophrenia and bipolar disorder, while ongoing research indicates promising neuroprotective qualities. APZ's mechanism of action, involving the regulation of neurotransmitter levels, appears to contribute to its potential to shield neural tissues from specific forms of harm and degeneration. Materials and Methods: To investigate its neuroprotective mechanisms, groups of rats were orally administered APZ at 1 or 2 mg/kg once daily for a 30-day period. In addition, neuronal toxicity was induced through intraperitoneal injection of four doses of lipopolysaccharide (LPS) at a concentration of 1 mg/kg. To evaluate cognitive function, particularly, short-term recognition memory, the procedure implemented the novel object recognition (NOR) task. Subsequently, brain tissues were gathered to examine markers linked with neuroinflammation, oxidative stress, and apoptosis. Results: The administration of LPS led to a decline in memory performance during the NOR tasks. Simultaneously, this LPS treatment raised inflammatory markers like cyclooxygenase (COX)-2, tumor necrosis factor (TNF)-α, and nuclear factor kappa B (NF-κB), increased oxidative markers such as malondialdehyde (MDA), and triggered apoptosis markers like Caspase-3 and Bcl2 associated X protein (Bax) within the brain. Furthermore, it decreased levels of antioxidants like reduced glutathione (GSH) and catalase, as well as the anti-apoptotic marker B-cell lymphoma (Bcl)-2 in brain tissue. The use of APZ resulted in enhanced recognition memory performance, as indicated by improved exploration and discrimination abilities of the objects in the NOR task. Moreover, APZ lowered the markers associated with neuronal vulnerability, such as COX-2, NF-κB, MDA, Caspase-3, and Bax. Additionally, it increased the levels of protective markers, including GSH, catalase, and Bcl-2 in LPS-challenged brains. Conclusions: In summary, the findings suggest that APZ exhibits protective properties against neuronal inflammation, oxidative stress, and apoptosis markers in the context of inflammatory-related neurodegeneration. Additional in-depth investigations are needed to further explore potential applications.

Treatment-emergent sexual dysfunction is frequently reported by individuals with major depressive disorder (MDD) on antidepressants, which negatively impacts treatment adherence and efficacy. We investigated the association of polymorphisms in pharmacokinetic genes encoding cytochrome-P450 drug-metabolizing enzymes, CYP2C19 and CYP2D6, and the transmembrane efflux pump, P-glycoprotein (i.e., ABCB1), on treatment-emergent changes in sexual function (SF) and sexual satisfaction (SS) in the Canadian Biomarker Integration Network in Depression 1 (CAN-BIND-1) sample. A total of 178 adults with MDD received treatment with escitalopram (ESC) from weeks 0-8 (Phase I). At week 8, nonresponders were augmented with aripiprazole (ARI) (i.e., ESC + ARI, n = 91), while responders continued ESC (i.e., ESC-Only, n = 80) from weeks 8-16 (Phase II). SF and SS were evaluated using the sex effects (SexFX) scale at weeks 0, 8, and 16. We assessed the primary outcomes, SF and SS change for weeks 0-8 and 8-16, using repeated measures mixed-effects models. In ESC-Only, CYP2C19 intermediate metabolizer (IM) + poor metabolizers (PMs) showed treatment-related improvements in sexual arousal, a subdomain of SF, from weeks 8-16, relative to CYP2C19 normal metabolizers (NMs) who showed a decline, F(2,54) = 8.00, p < 0.001, q = 0.048. Specifically, CYP2C19 IM + PMs reported less difficulty with having and sustaining vaginal lubrication in females and erection in males, compared to NMs. Furthermore, ESC-Only females with higher concentrations of ESC metabolite, S-desmethylcitalopram (S-DCT), and S-DCT/ESC ratio in serum demonstrated more decline in SF (r = -0.42, p = 0.004, q = 0.034) and SS (r = -0.43, p = 0.003, q = 0.034), respectively, which was not observed in males. ESC-Only females also demonstrated a trend for a correlation between S-DCT and sexual arousal change in the same direction (r = -0.39, p = 0.009, q = 0.052). CYP2C19 metabolizer phenotypes may be influencing changes in sexual arousal related to ESC monotherapy. Thus, preemptive genotyping of CYP2C19 may help to guide selection of treatment that circumvents selective serotonin reuptake inhibitor-related sexual dysfunction thereby improving outcomes for patients. Additionally, further research is warranted to clarify the role of S-DCT in the mechanisms underlying ESC-related changes in SF and SS. This CAN-BIND-1 study was registered on clinicaltrials.gov (Identifier: NCT01655706) on 27 July 2012.

BackgroundRisperidone ISM® is a newly developed long-acting injectable (LAI) treatment for schizophrenia in adults. In the absence of head-to-head comparisons with other similar antipsychotics, the objective of this study was to generate indirect evidence of some aspects of the safety and tolerability of Risperidone ISM compared to other LAI antipsychotics for treatment of patients with schizophrenia in the maintenance treatment setting.MethodsA literature review was conducted systematically to identify maintenance treatment studies reporting safety and tolerability outcomes for LAI antipsychotic therapies. Following an assessment of between-trial heterogeneity, a matching-adjusted indirect comparison (MAIC) was performed to account for between-trial imbalances in patient characteristics and to generate comparative evidence for safety and tolerability endpoints.ResultsThe analysis showed that incidence of extrapyramidal symptoms (EPS) was found to be numerically, but not statistically significantly, lower in patients receiving Risperidone ISM than in those receiving Paliperidone palmitate (PP) (OR [95% CI] 0.63 [0.29, 1.38], p = 0.253) and statistically significantly lower than with Aripiprazole monohydrate once-monthly (AOM) (OR [95% CI] 0.25 [0.12, 0.53], p < 0.001). Use of anticholinergic agents for the alleviation of EPS was also shown to be significantly lower in Risperidone ISM patients than in those receiving PP (OR [95% CI] 0.29 [0.10, 0.83], p = 0.021) or AOM (OR [95% CI] 0.01 [0.003, 0.06], p < 0.001), suggesting a superior tolerability profile for clinically relevant EPS. Results from the sensitivity analyses comparing stabilized and stable patients receiving Risperidone ISM to those receiving AOM yielded similarly favorable conclusions in line with the base case analyses.ConclusionsThis MAIC is consistent with the safety and tolerability results obtained during the PRISMA-3 clinical trial in the long-term treatment of schizophrenia and suggests a favorable safety and tolerability profile in terms of EPS incidence and anticholinergic agent use, relative to other antipsychotic therapies used for treatment of patients with schizophrenia in the maintenance setting.

The concurrent use of several medications is a common practice in the treatment of complex psychiatric conditions. One such commonly used combination is aripiprazole (ARI), an antipsychotic, and trazodone (TRZ), an antidepressant. In addition to their effects on dopamine and serotonin systems, both of these compounds are inhibitors of the 7-dehydrocholesterol reductase (DHCR7) enzyme. To evaluate the systemic and nervous system distribution of ARI and TRZ and their effects on cholesterol biosynthesis, adult mice were treated with both ARI and TRZ for 21 days. The parent drugs, their metabolites, and sterols were analyzed in the brain and various organs of mice using LC-MS/MS. The analyses revealed that ARI, TRZ, and their metabolites were readily detectable in the brain and organs, leading to changes in the sterol profile. The levels of medications, their metabolites, and sterols differed across tissues with notable sex differences. Female mice showed higher turnover of ARI and more cholesterol clearance in the brain, with several post-lanosterol intermediates significantly altered. In addition to interfering with sterol biosynthesis, ARI and TRZ exposure led to decreased ionized calcium-binding adaptor molecule 1 (IBA1) and increased DHCR7 protein expression in the cortex. Changes in sterol profile have been also identified in the spleen, liver, and serum, underscoring the systemic effect of ARI and TRZ on sterol biosynthesis. Long-term use of concurrent ARI and TRZ warrants further studies to fully evaluate the lasting consequences of altered sterol biosynthesis on the whole body.

Aripiprazole (ARP) is an atypical neuroleptic used in the therapy of mental diseases such as schizophrenia. The lack of optimal adherence to an oral therapy regime creates the basis for designing ARP long-acting injections. This study aimed to use 105 °C hot melt extrusion (HME) as a formulation method for rods based on poly(d,l-lactide-co-glycolide-co-trimethylene carbonate) with a molecular weight (Mn) of 21 kDa (Td,l 21), poly(l-lactide-co-glycolide-co-trimethylene carbonate) with a Mn of 59 kDa (Tl 59), and with a Mn of 77 kDa (Tl 77). The following methods were involved in the research: NMR, DSC, XRD, HSM, FTIR, GPC, SEM, and mechanical tests. HME at 105 °C (i) ensured flow behavior for terpolymers, (ii) did not influence the terpolymers’ composition and (iii) the polymorph changes of ARP, and (iv) resulted in the changes in terpolymers’ Mn. For the rods with ARP based on Td,l 21 (Td,l 21 rod-ARP) and Tl 59 (Tl 59 rod-ARP), plasticization was noted. No drug–terpolymer interactions were revealed. No pores were observed on the surface. Due to its high flexibility and rubber character, Td,l 21 rod-ARP may be proposed for intramuscular administration, whereas Tl 59 rod-ARP, due to its higher strength and moderate stiffness, is proposed for subcutaneous administration.

Aripiprazole combined with nerve growth factor improves cognitive function in mice with schizophrenia model

Several studies have reported that a switch to the dopamine partial agonist (DPA) aripiprazole (ARP), especially when the switch is abrupt, is likely to fail and sometimes worsen psychosis in schizophrenia patients already under high-dose antipsychotic treatment. Such a switching failure is speculated to be related to be the dopamine supersensitivity state. The risks of switching to the DPA brexpiprazole (BREX) have not been reported. We retrospectively analyzed the cases of 106 patients with schizophrenia to identify any factors related to the success or failure of switching to BREX. The comparison between the patients with dopamine supersensitivity psychosis (n = 44) and those without (n = 62) revealed no significant difference in the switching failure judged at the sixth week. A comparison of the patients with successful switching (n = 80) and those who failed (n = 26) revealed that patients with treatment-resistant schizophrenia (TRS) were significantly more likely to fail. A logistic regression analysis also revealed that patients with past failure of switching to ARP are likely to succeed in switching to BREX. The 2-year follow-up of the patients with successful switching to BREX suggested that the patients who were treated with BREX, even temporarily, experienced some improvement in their Global Assessment of Functioning and Clinical Global Impression-Severity scores. Overall, the results indicate that patients with schizophrenia can be switched more safely to BREX compared to ARP. However, the failure of switching to BREX could be higher in patients with TRS, and thus, starting BREX treatment in refractory patients warrants careful monitoring.

Thermodynamic analysis and molecular dynamic simulation of solid–liquid equilibrium behavior of antipsychotic drug aripiprazole (Form III) in three binary solvent mixtures

To evaluate the relationship between daily doses of antipsychotic drugs, their serum concentrations, and characteristics of patients treated for schizophrenia or schizophreniform disorder in day-to-day clinical practice. A total of 187 patients were included in the study, 77 (41.1%) patients were on monotherapy, and 110 (58.9%) patients received two or more antipsychotics. Patients age was 27.8±8.1 years, and their body weight was 79.8±15.6 kg. The sample was represented mainly by young men (93.0%). The proportion of smokers was 37.4%. The appropriate HPLC-MS/MS method was used for the simultaneous analysis of 8 antipsychotics and its active metabolites. Serum concentrations of the drugs aripiprazole (ARI), chlorpromazine (CPZ), haloperidol (HAL), zuclopenthixol (ZUC), clozapine (CLO), risperidone (RIS), quetiapine (QUE), olanzapine (OLA), norclozapine (N-desmethylclozapine, NOR), 9-hydroxyrisperidone (9-OH-RIS), dehydroaripiprazole (DGA) were measured. The serum concentration/dose ratio (C/D) was employed as the primary outcome measure, as doses were not kept constant during the study. The active antipsychotic fraction (drug+active metabolite, active moiety - AM) was also evaluated for RIS and ARI. In addition, the metabolite/parent ratio (MPR) was evaluated for RIS and ARI. A total of 265 biological samples were obtained, 421 and 203 measurements of the concentration of drugs and their metabolites were carried out, respectively. Overall, 48% of antipsychotics levels were in the expected therapeutic ranges, 30% were below therapeutic ranges, and 22% were above them. A total of 55 patients underwent dose adjustments or drug changes due to ineffectiveness or side-effects. It has been found that smoking reduces the level of C/D for CLO (p<0.01, Mann-Whitney test). We have established that comedication with CLO significantly increases the C/D ratio of QUE (p<0.05, Mann-Whitney test). We have not revealed any influence of weight and age of the subjects on the C/D. The dose-concentration regression relationships are formalized for all AP. Therapeutical drug monitoring (TDM) is an essential tool to personalize antipsychotic therapy. Careful analysis of TDM data can contribute significantly to the study of the impact of individual patient characteristics on systemic exposure to these drugs.

Good adherence to medication is critical for successfully treating psychiatric disorders. Tailor-made pharmaceutical formulations can provide a suitable dosage form to meet the specific needs of individual patients who exhibit poor adherence to industrially manufactured products. Herein, we prepared aripiprazole (ARP) gummies (ARP-Gs) using a commercially available ARP formulation. We aimed to clarify the palatability of ARP-Gs by performing a gustatory sensation test in healthy volunteers. We performed two types of organoleptic masking of ARP-Gs, cocoa- and fruit-flavoured gummies (6.0 mg of ARP/3.5 g of gummy), and conducted two different gustatory sensation tests for each ARP-G. Ten young, healthy volunteers (mean ± standard deviation, 23.7 ± 1.2 years) were enrolled in each trial. The overall palatability of ARP-Gs was evaluated using the 100-mm visual analogue scale (VAS). Receiver operating characteristic (ROC) curve analysis was performed between VAS scores of total ARP-G palatability and acceptability assessed using a 5-point rating scale. Among cocoa-flavoured ARP-Gs, those combining aspartame, cocoa powder, and banana flavour (ABC-ARP-G) exhibited the highest VAS scores for total palatability. Similarly, the VAS scores of grapefruit-flavoured ARP-Gs (GF-ARP-G) showed the highest values considering all fruit-flavoured ARP-Gs. The VAS scores for ABC-ARP-G and GF-ARP-G greatly exceeded the cut-off values of acceptability calculated using the ROC curve. We developed two types of ARP-Gs with organoleptic masking as tailor-made pharmaceutical formulations. ABC-ARP-Gs and GF-ARP-Gs could be acceptable in patients. ARP-Gs could be an alternative to currently available pharmaceutical formulations to enhance their adherence and meet the specific needs of individual patients.

Based on their proven anti-inflammatory and antioxidant effects, recent studies have examined the therapeutic potential of the sodium-glucose cotransporter 2 (SGLT2) inhibitors in neurodevelopmental disorders such as autism spectrum disorder (ASD). Therefore, the aim of this study is to assess the effects of subchronic systemic treatment with intraperitoneal (i.p.) canagliflozin (20, 50, and 100 mg/kg) compared to aripiprazole (ARP) (3 mg/g, i.p.) in a valproic acid (VPA)-induced rat model of autism. The behavioral characteristics of ASD, oxidative stress, and acetylcholinesterase (AChE) activity in rats with ASD-like behaviors, which were induced by prenatal exposure to VPA, were evaluated. The behavioral assessment methods used for this study were the open field test (OFT), the marble-burying test (MBT), and the nestlet-shredding test (NST) to examine their exploratory, anxiety, and compulsiveness-like actions, while the biochemical assessment used for this study was an ELISA colorimetric assay to measure ASD biomarker activity in the hippocampus, prefrontal cortex, and cerebellum. Rats that were pretreated with 100 mg/kg of canagliflozin displayed a significantly lower percentage of shredding (1.12 ± 0.6%, p < 0.01) compared to the ARP group (3.52 ± 1.6%). Pretreatment with (20 mg/kg, 50 mg/kg, and 100 mg/kg) canagliflozin reversed anxiety levels and hyperactivity and reduced hyper-locomotor activity significantly (161 ± 34.9 s, p < 0.05; 154 ± 44.7 s, p < 0.05; 147 ± 33.6 s, p < 0.05) when compared with the VPA group (303 ± 140 s). Moreover, canagliflozin and ARP mitigated oxidative stress status by restoring levels of glutathione (GSH) and catalase (CAT) and increasing the levels of malondialdehyde (MDA) in all tested brain regions. The observed results propose repurposing of canagliflozin in the therapeutic management of ASD. However, further investigations are still required to verify the clinical relevance of canagliflozin in ASD.

The low water solubility of an active pharmaceutical ingredient (aripiprazole) is one of the most critical challenges in pharmaceutical research and development. This antipsychotic drug has an inadequate therapeutic impact because of its minimal and idiosyncratic oral bioavailability to treat schizophrenia. The main objective of this study was to improve the solubility and stability of the antipsychotic drug aripiprazole (ARP) via forming binary as well as ternary inclusion complexes with hydroxypropyl-β-cyclodextrin (HPβCD) and L-Arginine (LA) as solubility enhancers. Physical mixing and lyophilization were used in different molar ratios. The developed formulations were analyzed by saturation solubility analysis, and dissolution studies were performed using the pedal method. The formulations were characterized by FTIR, XRD, DSC, SEM, and TGA. The results showcased that the addition of HPβCD and LA inclusion complexes enhanced the stability, in contrast to the binary formulations and ternary formulations prepared by physical mixing and solvent evaporation. Ternary formulation HLY47 improved dissolution rates by six times in simulated gastric fluid (SGF). However, the effect of LA on the solubility enhancement was concentration-dependent and showed optimal enhancement at the ratio of 1:1:0.27. FTIR spectra showed the bond shifting, which confirmed the formation of new complexes. The surface morphology of complexes in SEM studies showed the rough surface of lyophilization and solvent evaporation products, while physical mixing revealed a comparatively crystalline surface. The exothermic peaks in DSC diffractograms showed diminished peaks previously observed in the diffractogram of pure drug and LA. Lyophilized ternary complexes displayed significantly enhanced thermal stability, as observed from the thermograms of TGA. In conclusion, it was observed that the preparation method and a specific drug-to-polymer and amino acid ratio are critical for achieving high drug solubility and stability. These complexes seem to be promising candidates for novel drug delivery systems development.

The screening of multicomponent crystal system (MCC) is a key method for improving physicochemical properties of active pharmaceutical ingredients (APIs). The challenges associated with experimental salt screening include a large number of potential counterions and solvent systems and tendency to undergo disproportionation to produce free form during crystallization. These challenges may be mitigated by a combination of experimental and computational approaches to salt screening. The goal of this study is to evaluate performance of the counterion screening methods and propose and validate novel approaches to virtual solvent screening for MCC crystallization. The actual performance of the ΔpKa > 3 rule for counterion selection was validated using multiple screenings reports. Novel computational models for virtual solvent screening to avoid MCC incongruent crystallization were proposed. Using the ΔpKa rule, 10 acid counterions were selected for experimental aripiprazole (APZ) salt screening using 10 organic solvents. The experimental results were used to validate the proposed novel virtual solvent screen models. Experimental APZ salt screening resulted in a total of eight MCCs which included glucuronate, mesylate, oxalate, tartrate, salicylate and mandelate. The new model to virtually screen solvents provided a general agreement with APZ experimental findings in terms of selecting the optimal solvent for MCC crystallization. The rational selection of counterions and organic solvents for MCC crystallization was presented using combined novel computational model as well as experimental studies. The current virtual solvent screen model was successfully implemented and validated which can be easily applied to newly discovered APIs.

An effective pretreatment technique based on multi-walled carbon nanotubes to reduce the matrix effect in plasma samples analyzed by a new type probe electrospray ionization method

In vitro dissolution that predicts the in vivo performance of solid preparations is extremely important in formulation optimization. Fraction absorbed (Fa) has been used to screen in vitro dissolution protocols based on the idea of in vitro-in vivo correlation (IVIVC) but failed to increase the success rate due to the inaccuracy of the Fa. The essence of IVIVC is the correlation between in vitro dissolution and in vivo dissolution. We tried to establish in vitro dissolution protocol via similarity with in vivo dissolution using aripiprazole (APZ) as a model drug. Hybrid APZ crystals (APZ-HCs) were prepared by physically embedding aggregation-caused quenching (ACQ) fluorophores inside the lattice to measure the in vivo dissolution. The process did not change the physicochemical properties and crystallinity of APZ. The fluorophore illuminated APZ crystals but was quenched upon dissolution of APZ-HCs in aqueous media, enabling monitoring intact APZ-HCs in real-time. The good correlation between fluorescent quenching and dissolution of APZ-HCs justified reliable quantification of intact APZ crystals. The residual percentage of fluorescence intensity in rats treated by APZ-HCs was recorded with time, which was converted to in vivo dissolution by the difference from 100%. The in vivo dissolution was validated with the Fa. The in vitro dissolution profile of APZ was set up via a similarity factor larger than 50 in comparison with the in vivo dissolution. The study provides a novel idea and method to establish in vitro dissolution protocol.